The success of mammalian pregnancy is inherently dependent upon maternal immunological tolerance of the genetically foreign fetus. Understanding the mechanism of this tolerance can contribute to the prevention of early pregnancy loss and pre-natal disease, and suggest new methods for contraception. This project is designed to contribute to the long-term goal of elucidating the immunological mechanisms of maternal-fetal tolerance. It focuses on the peripheral modulation of cell-mediated immunity that has been observed during pregnancy in the horse and other species. The hypothesis to be tested is that pregnancy induces systemic tolerance in the CD4+ T cell population of the pregnant mare in a manner that is not specific for paternal alloantigen. By establishing pregnancies of differing genetic compatibilities and examining the maternal immune response, this project will investigate the following specific aims: 1. To determine the antigen specificity of the T cell impairment observed during the pregnant state. 2. To determine the respective contributions of the CD4+ and CD8+ lymphocyte subsets to the defect in cytotoxic T lymphocyte activity. Techniques to be utilized in this project include: flow cytometry, enzyme-linked immunosorbant assays (ELISA), reverse-transcriptase real-time polymerase chain reaction, cell sorting, and cytotoxic T lymphocyte (CTL) killing assays. This project takes advantage of the naturally occurring modulation of maternal immunity in equine pregnancy that offers unique insights into the fetal-maternal immunological relationship in mammals. This research will help advance the understanding of why a fetus is accepted by the mother's immune system. It will provide valuable information that will contribute to the fields of infertility and contraception. Furthermore, the immunological concepts surrounding this process are also relevant to the fields of transplantation biology, cancer, and infectious diseases.